Abstract
The search for a reliable, early-disease biomarker for Parkinson’s disease (PD) that reflects underlying pathology is a high priority in PD research. Salivary alpha-synuclein (α-Syn) is an easily accessible biomarker for PD with promising results. Our aim was to evaluate the performance of salivary α-Syn as a diagnostic biomarker of PD. We identified 476 studies through a systematic literature review according to PRISMA guidelines. Finally, eight studies reporting data on salivary α-Syn were included in the review (1240 participants). The quality of studies was assessed by Newcastle–Ottawa scale. (1) Three studies showed that the total α-Syn levels were significantly lower in PD patients compared to healthy controls, while in another five there was no significant association. (2) In some studies, total salivary α-Syn was associated with demographic and clinical features; however, no consistent pattern emerged. In one study, total α-Syn levels were associated with poor cognitive performance in PD patients. (3) Four studies showed a higher salivary oligomeric α-Syn and oligomeric α-Syn/total α-Syn ratio in PD compared to healthy controls, while in another four there was no association. (4) One study concluded that genetic polymorphisms may influence total salivary α-Syn in PD patients. Taken together, the potential of salivary total α-Syn as a PD biomarker is still uncertain, whereas salivary oligomeric α-Syn appears quite promising. Pre-analytical and analytical factors of included studies were important limitations to justify the introduction of salivary α-Syn into clinical practice.
Similar content being viewed by others
References
Al-Nimer MS, Mshatat SF, Abdulla HI (2014) Saliva alpha-synuclein and a high extinction coefficient protein: a novel approach in assessment biomarkers of Parkinson’s disease. N Am J Med Sci 6:633–637. https://doi.org/10.4103/1947-2714.147980
Barbour R et al (2008) Red blood cells are the major source of alpha-synuclein in blood. Neuro-degener Dis 5:55–59. https://doi.org/10.1159/000112832
Bollero P, Franco R, Cecchetti F, Miranda M, Barlattani A Jr, Dolci A, Ottria L (2017) Oral health and implant therapy in Parkinson’s patients: review. ORAL Implantol 10:105–111. https://doi.org/10.11138/orl/2017.10.2.105
Bougea A, Stefanis L, Paraskevas GP, Emmanouilidou E, Vekrelis K, Kapaki E (2019) Plasma alpha-synuclein levels in patients with Parkinson’s disease: a systematic review and meta-analysis. Neurol Sci. https://doi.org/10.1007/s10072-019-03738-1
Campo F, Carletti R, Fusconi M, Pellicano C, Pontieri FE, Di Gioia CR, de Vincentiis M (2018) Alpha-synuclein in salivary gland as biomarker for Parkinson’s disease. Rev Neurosci. https://doi.org/10.1515/revneuro-2018-0064
Cao Z, Wu Y, Liu G, Jiang Y, Wang X, Wang Z, Feng T (2018) alpha-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson’s disease. Neurosci Lett 696:114–120. https://doi.org/10.1016/j.neulet.2018.12.030
Cersosimo MG, Benarroch EE (2012) Pathological correlates of gastrointestinal dysfunction in Parkinson’s disease. Neurobiol Dis 46:559–564. https://doi.org/10.1016/j.nbd.2011.10.014
Del Tredici K, Hawkes CH, Ghebremedhin E, Braak H (2010) Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol 119:703–713. https://doi.org/10.1007/s00401-010-0665-2
Devic I et al (2011) Salivary alpha-synuclein and DJ-1: potential biomarkers for Parkinson’s disease. Brain 134:e178. https://doi.org/10.1093/brain/awr015
Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a frontal assessment battery at bedside. Neurology 55:1621–1626
El-Agnaf OM et al (2006) Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J 20:419–425. https://doi.org/10.1096/fj.03-1449com
Goetz CG et al (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170. https://doi.org/10.1002/mds.22340
Goldman JG et al (2018) Cerebrospinal fluid, plasma, and saliva in the BioFIND study: relationships among biomarkers and Parkinson’s disease Features. Mov Disord. 33:282–288. https://doi.org/10.1002/mds.27232
Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442
Hong Z et al (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133:713–726. https://doi.org/10.1093/brain/awq008
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
Kang WY et al (2014) Salivary DJ-1 could be an indicator of Parkinson’s disease progression. Front Aging Neurosci 6:102. https://doi.org/10.3389/fnagi.2014.00102
Kang W et al (2016) Salivary total alpha-synuclein, oligomeric alpha-synuclein and SNCA variants in Parkinson’s disease patients. Sci Rep 6:28143. https://doi.org/10.1038/srep28143
Lin X et al (2012) DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease. Sci Rep 2:954. https://doi.org/10.1038/srep00954
Litvan I et al (2003) Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 18:467–486. https://doi.org/10.1002/mds.10459
Mata IF et al (2010) SNCA variant associated with Parkinson disease and plasma alpha-synuclein level. Arch Neurol 67:1350–1356. https://doi.org/10.1001/archneurol.2010.279
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097
Nasreddine ZS et al (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.x
Parnetti L, Castrioto A, Chiasserini D, Persichetti E, Tambasco N, El-Agnaf O, Calabresi P (2013) Cerebrospinal fluid biomarkers in Parkinson disease Nature reviews. Neurology 9:131–140. https://doi.org/10.1038/nrneurol.2013.10
Simonsen AH et al (2016) The utility of alpha-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature. Biomark Med 10:19–34. https://doi.org/10.2217/bmm.14.105
Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95:6469–6473
Stang A (2010) Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z
Stewart T et al (2014) Cheek cell-derived alpha-synuclein and DJ-1 do not differentiate Parkinson’s disease from control. Neurobiol Aging 35:418–420. https://doi.org/10.1016/j.neurobiolaging.2013.08.008
Vivacqua G et al (2016) Abnormal salivary total and oligomeric alpha-synuclein in Parkinson’s disease. PLoS One 11:e0151156. https://doi.org/10.1371/journal.pone.0151156
Vivacqua G et al (2019) Salivary alpha-synuclein in the diagnosis of Parkinson’s disease and progressive supranuclear palsy. Parkinsonism Relat Disord. https://doi.org/10.1016/j.parkreldis.2019.02.014
Yu S et al (2007) Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience 145:539–555. https://doi.org/10.1016/j.neuroscience.2006.12.028
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Bougea, A., Koros, C. & Stefanis, L. Salivary alpha-synuclein as a biomarker for Parkinson’s disease: a systematic review. J Neural Transm 126, 1373–1382 (2019). https://doi.org/10.1007/s00702-019-02062-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-019-02062-4